Aryl mercury compounds of ureid



Reissued Oct. 11, 1938 PATENT OFFICE 20,880 I ARYL MERCURY COMPOUNDS OFUREID' AND PURINE BASES AND DTETHOD MAKING THE SAlVIE Carl N. Andersen,Welle sleyHilla-Mass assignor to Lever Brothers Company, a. corporationof Maine No Drawing. Original No. 2,118,133, dated May 24, 1938,Serial'No. 754,373, November 22, 1934, Applicationifor reissue July-30,1938, Serial No.

The present invention relates to the production of certain new organicmercury compounds.

It is an object of my invention to produce new aryl mercury compounds ofureid and purine bases useful as germicides and for othertherapeutic-purposes.

More particularly, it is an object of my invention to prepare certainorganic mercury compounds which may be regarded as derivatives of animido compound, in which the imido group is a part of the characteristicgroup:

}I .H i N-HI This group is contained in the ureids and bases.

I have discovered that when the hydrogen atom or atoms of this group arereplaced by the essential radical of certain aromatic mercury compounds,compounds are produced which have extraordinarily high potency asantiseptics and germicides and at the same time are characterized byrelatively low toxicity and other desirable properties.

The compounds constituting the subject matter of the present inventioninclude those having the general formula (13:0 I NHgR a in which Rrepresents an aromatic structure to a nuclear carbon'atom of which themercury is directly attached.

Compounds included in my invention may also have one of the imidohydrogen, atoms replaced by a monovalent hydrocarbon radical such as:

-NHgR i N; I where X is any mono-valent radical.

Similarly, the oxygen may be replaced by sulphur to form the radical: w

1| T HgR purine In the above description it is assumed that 15 Claims.(01; 260442) when the compound contains two imido hydrogens, both willbe replaced. By employing suitable amounts of reagents and under properconditions, only one may be replaced and I intend my invention toinclude compounds of this type, for example:

NHgR

0L0 l H More particularly, R represents an aromatic structure, which maybe an aromatic nucleus with or without side chains, and the expressionaromatic structure used herein is intended to be generic and include anaromatic nucleus with or without side chains. The aromatic structure isof the type'in which none of the nuclear or side chain carbon atoms hasdirect linkage with any element other than hydrogen, carbon or mercury.R may stand for the phenyl group, CsHs, or for an aromatic hydrocarbonhaving a nucleus similar to the phenyl hydrocarbons, as for example,polycyclic hydrocarbons, in which all of the nuclear carbon atoms, otherthan the one attached to mercury, and any side chain carbon atoms, havetheir valences satisfied either by carbon or hydrogen. Examples are thediphenyl, tolyl, xylyl, and naphthyl groups.

I have investigated many compounds containing the above describedcharacteristic group and have discovered that they may be converted intoaromatic mercury compounds of the type described. I have prepared asufiiciently large number to lead me to believe that all of thecompounds containing this characteristic group can be converted intoaromatic mercury derivatives of the type described, and I intend myinvention to be generic to include this entire class. I' have preparedaromatic mercury derivatives of the following members of this class anddetermined their physical properties. They are representative of theentire class and all are useful as antisepticsand germicides: barbituricacid, diethyl barbituric acid, parabanic acid, thiobarbituric acid, uricacid, di-chlorobarbituric acid, alloxan, theobromine, allantoin,xanthine, Benzo Fast Orange W S D (Schultz. #305, 7th ed), and AlgolYellow (Schultz #1250 Colour Index #1138) The theobromine and xanthineare derivatives of the purine group. They are sometimes spoken of asaliphatic alkaloids, but more accurately as vegetable bases.

Many dyes, such as the last two compounds listed contain the abovereferred to characteristic In my application Serial No. 754,372, filedNovember 22, 1934, I have disclosed the general method of preparing anaromatic mercury imido compound by reacting a compound containing an Iimido group with an aromatic mercury hydrox- 3 ide. In my applicationSerial No. 694,200, filed October 18, 1933, I have disclosed the generalmethod of preparing an aromatic mercury imido compound by reacting acompound containing an imido group with a soluble aromatic mercury salt,such as the acetate. In each method, the aromatic mercury radical of thehydroxide or the salt becomes attached to the nitrogen of the imidogroup. Either of these general methods may be employed in producing thecompounds comprising the present invention.

The compounds may be prepared in various ways. The following specificexamples are given as illustrative of the methods which may be employedin producing my compounds, as well as to illustrate representativeorganic mercury derivatives of imido compounds falling within the scopeof my invention:

Example 1 5.88 grams of phenylmercury hydroxide is dissolved in 2 litersof water by heating to boiling. The solution is then filtered to removeany gums or other insoluble materials present. To the filtrate is added3.2 grams of barbituric acid dissolved in cc. of water. A precipitateforms immediately. The mixture is allowed to stand for 12 hours, andfiltered. The precipitate is washed thoroughly with warm water and driedin an oven at C. The resulting product is a white crystalline powderwhich is sparingly soluble in water. The melting point is in excess of270 C. The compound is phenylmercury barbiturate.

Example 2 17.64 grams of phenylmercury hydroxide is dis 17.64 grams ofphenylmercury hydroxide is dissolved in 4 liters of water and heateduntil solution is complete. The solution is then filtered to remove anygum or undissolved material. To the filtrate is added 4.75 grams ofthiobarbituric acid in 400 cc. of water. A precipitate results and themass is allowed to stand until cool, when it is filtered, washed withwarm water and dried. The

precipitate does not melt at 250 C. The compound is phenylmercurythiobarbiturate.

Example 4 3.3 grams of phenylmercury acetate is dissolved in 200 cc. ofwater and heated until solution is complete. The solution is thenfiltered to remove any insoluble material. To the filtrate is added the.5 gram of xanthine dissolved in alcohol. The solution is concentratedto of its volume and allowed to stand for 18 hours. A precipitateresults and the solution is filtered. The precipitate is washed wellwith warm water and a few cc. of alcohol, and dried. It decomposes at360 C. The compound is phenylmercury xanthine.

Example 5 17.64 grams of phenylmercury hydroxide is dissolved in 2liters of water and heated until solution is complete. The solution isfiltered to remove any insoluble material. To the filtrate is added 3.16grams of allantoin dissolved in 50 cc. of alcohol. A precipitate resultsand after the mixture has been allowed to stand for some time it isfiltered. The precipitate is washed well with warm water and a few cc.of alcohol and dried. It decomposes at 210 C. The compound isphenylmercury allantoin.

Example 6 3.36 grams of phenylmercury acetate is dissolved in 200 cc. ofwater and heated until solution is complete. The solution is filtered toremove any insoluble material. To the filtrate is added 1.98 grams oftheobromine dissolved in 200 cc. of water. A starch-like jelly resultson standing. Upon concentrating the mixture a precipitate separateswhich is removed by filtration, washed and dried. It melts at 248-250 C.and is phenylmercury theobromine.

From the description of the specific examples it will be readilyapparent to one skilled in the art how other compounds containing thecharacteristic group may be reacted with an aromatic mercury compound toproduce aromatic mercury imides of analogous structure.

The reacting materials are employed in theoretical quantities. In somecases, particularly where the imido compound is water-soluble, I mayemploy approximately 10% excess of the imido compound in order to insurecomplete conversion of the aromatic mercury compound.

The operativeness of the process is not found to depend in any degreeupon the temperature in which the reaction is efl'ected. It isconvenient to use heat because it facilitates the solution of thereacting components and speeds the reaction but the process can becarried out at any temperature, for example, room temperature. larly,the process may be carried out in any mutual solvent. Water is usuallyemployed for reasons of convenience if the reacting components are watersoluble, but if not, other solvents such as the alcohols or acetone ormixtures of these with each other or alone, may be used.

' All of the compounds produced as above described are characterized byextraordinarily high potency as germicides. Tests to determine theirefficacy in killing B. typhosus and Staph. aureus were carried on underthe following conditions:

Aqueous solutions of varying dilutions from 1:10,000 upward untilkilling ceased, were made These dilutions were employed in the conductof the tests by the following methods:

Circular 198, U. S. Dept. of Agriculture, Dec.

Simi- 1931, described as F. D. A. Method Against Eberthella typhi(typhoid bacillus) at 37 C. and F. D. A. Special Method Against Staph.aureus at 37 C. I

As illustrative of the potency of the compounds, the killing power ofthe following compounds is given merely as illustrative:

The figures represent the maximum dilutions at which killing in 15minutes resulted:

These compounds are further characterized by particularly desirableproperties from the standpoint of relative freedom from toxicity andtheir adaptability for various germicidal and therapeutic uses. Testsmade with some of them, for example, the barbiturate, indicate that theyare not only especially well suited for use as a germicide, but alsothat they have many other uses in medicine, for example, they may beused as a hypnotic or as a sedative and may be administered internally,intravenously or peritoneally with excellent results.

All of these compounds retain a high germicidal value when incorporatedin soaps or mixed in various menstruums in forming antiseptic andgermicidal compositions.

These new compounds may be used directly as germicides in aqueous orother solutions or may be formed into various preparations such as mouthwashes, tooth pastes, soaps, ointments, etc.

This application is a continuation in part of my earlier filedapplication, Serial Number 694,203, filed October 18, 1933.

I claim:

1. A new organic mercury compound of the general formula (RHg)2.R1 inwhich R represents an aromatic structure in which none of the carbonatoms has direct linkage with any element other than hydrogen, carbonand mercury; and'in which R1 represents the radical of a compoundselected from the group consisting of ureids and purine bases, the RHggroups being linked to said radical by the replacement of imidohydrogen.

2. A new organic mercury compound of the general formula (RHg):c.R1, inwhich R represents an aromatic structure to a carbon atom of which themercury is directly attached and in which none of the carbon atoms hasdirect linkage with any element other than hydrogen, carbon and mercury;in which at represents the number of RHg groups in the compound and isan integer having a value of at least one and not more than two; and inwhich R1 represents the radical of a compound selected from the groupconsisting of ureids and purine bases, the RHg group being linked tosaid radical by the replacement of imido hydrogen.

3. A new organic mercury compound of the general formula RHg.R1, inwhich R represents an aromatic structure to a carbon atom of which themercury is directly attached and in which none of the carbon atoms hasdirect linkage with any element other than hydrogen, carbon and mercury;and in which R1 represents the radical of a compound selected from thegroup consisting of ureids and purine bases, one of the imido hydrogensthereof being replaced by the RHg group.

4. A new organic mercury compound of the general formula RHg.R1 in whichR represents an aromatic structure to a carbon atom of which the mercuryis directly attached and in which none of the carbon atoms has directlinkage with any element other than hydrogen, carbon and mercury; and inwhich R1 represents the radical of a compound selected from the groupconsisting of ureids and purine bases, one of the imido hydrogensthereof being replaced by a monovalent lower alkyl radical and the otherimido hydrogen thereof being replaced by the RHg group.

5. A compound of the general formula (RHg):z:.R1, in which R representsan aromatic structure in which none of the carbon atoms have directlinkage with any element other than hydrogen, carbon and mercury; inwhich a: represents the number of RHg groups in the compound and is aninteger having a value of at least 1 and not more than 2, and in whichR1 represents a barbituric acid radical.

6. A new organic mercury compound of the general formula (C6H5Hg)a:-R1,in which a: represents the number of CsHsHg groups in the compound andis an integer having a value of at leastone and not more than two, andin which R1 represents the radical of a compound selected from the groupconsisting of ureids and purine bases, the CsHsHg group being linked tosaid radical by the replacement of imido hydrogen.

7. A compound of the (CEHSHgJLRI in which n: represents the number ofCeHsI-Ig groups in the compound and is an integer having a value of atleast 1 and not more than 2 and in which R1 represents the radical ofbarbituric acid.

8. A phenylmercury xanthine.

9. A new organic mercury compound of the general formula C6H5Hg.R1, inwhich R1 represents the radical of a compound selected from the groupconsisting of ureids and purine bases, one of the imido hydrogensthereof being replaced by the C6H5Hg group.

10. Phenylmercury theobromine.

11. The method of preparing phenylmercury barbiturate which comprisesreacting, in solution, barbituric acid with the compound C6H5HgOH.

12. The method of preparing organic mercury compounds which comprisesreacting, in solution,

a compound selected from the group consisting of ureids and purine baseswith an aromatic mercury hydroxide in which the mercury is directlyconnected to a carbon atom of an aromatic structure in which none of thecarbon atoms has direct linkage with any element other than hydrogen,carbon and mercury, whereby the aromatic mercury radical replaceshydrogen in the general formula compounds which comprises reacting, insolution, a compound selected from the group consisting of ureids andpurine bases with the compound CeHsHgOH.

15. A new organic mercury compound of the general formula (CsH5Hg)2.R1,in which R1-rep resents-the radical of a compound selected from thegroup consisting of ureids and purine bases, the CsHsI-Ig groups beinglinked to said radical by the replacement of imido hydrogens.

, ,CARL N. ANDERSEN.

